Purpose:
Mutations in the ABCA4 gene can cause autosomal recessive Stargardt disease (STGD), cone or cone-rod dystrophy (CRD), and retinitis pigmentosa. The objective of this study was to find the possible disease causing variants of ABCA4 gene in a cohort of Chinese patients with STGD or CRD and described the correlation between the phenotype and genotype.

Methods:
A total of 161 probands were recruited for genetic analysis; these included 111 patients diagnosed with STGD and 50 individuals with CRD. All probands underwent ophthalmic examinations including best corrected visual acuity, fundus examination, optical coherence tomography, fundus autofluorescence, and electroretinograms. Genomic DNA was extracted from venous blood of all participants and all coding exons and exon-intron boundaries of the ABCA4 gene were screened for mutations by PCR-based DNA sequencing, followed by analyses for pathogenicity by in silico programs. Restriction fragment length polymorphism analysis or allele specific PCR was used to validate the substitution in all available family members.<br />

Results:
We found at least two disease-causing alleles in 90 unrelated patients (56%), one disease-causing allele in 23 patients (14%), and no disease-causing allele in 58 affected individuals (30%). In total, 122 disease-causing variants of the ABCA4 gene, including 72 novels, were identified. The identified mutations included 69 (56.7%) missense, 15 (12.3%) nonsense, 21 (17.2%) splicing effect, and 17 (13.9%) indel mutations. The most frequent mutation in this cohort was c.2424C>G p.Y808X, representing 7.2% of all disease alleles. 102 (102/111, 92%) STGD patients were found carrying two or one disease-causing allele of the ABCA4 gene, however, only 11 (11/50, 22%) patients with CRD were identified harboring two or one disease-causing allele.

Conclusions:
Our results further confirmed that the ABCA4 gene is the most common disease-causing gene for Chinese patients with autosomal recessive STGD. The mutation spectrum of the ABCA4 gene is different from the ones of Caucasian patients.